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FILE NAME Talc TALC DATE 1997 DOC TALC026 DOCUMENT DESCRIPTION Journal Article - Perineal Powder Exposure and the Risk of Ovarian Cancer OO suppl 6 of automoers in New ty of filling h 1994 NE American Journal of Epidemiology NENE Copyright '1997 by The Johns Hopkins University School of Hygiene and Public Health All rights reserved SSS SSS Perineal Powder Exposure and the Risk of Ovarian Cancer Vol 145 No. 5 Printed in U.S.A. sea ceaseeenes exposure to ocytic leu- te myeloid nded case- zukemia in sel Eur J gasoline in III Thorpe oxicology Princeton 12 A chronic ' Am Coll related : 1985 ell cancer nd J Work s between d liquids Linda S. Cook Mary L. Kamb and Noel S. Weiss This control study evaluated the risk of epithelial ovarian cancer associated with various forms of powder application Cases included all genital exposure to women aged 20-79 years in three counties of western Washington who were diagnosed with borderline or invasive ovarian cancer from 1986 of eligible cases were interviewed A sample of similarly aged women who lived in thestehrcoouugnhti1e9s8i8de6nt4if.ie3d by random digit dialing served as controls The overall response among control women was 68.0 Information on powder application and other potential risk factors was ascertained during the person interview Overall ovarian cancer cases n = 313 were more likely than controls n = 422 to ever have used powder adjusted relative risk RR = 1.5 95 confidence interval CI 1.1-2.0 After adjustment for and other methods of genital powder application none vs. any an elevated relative risk of age ovarian cancer was noted only for women with a history of perineal dusting RR = 1.6 95 CI 1.1-2.3 or use of genital deodorant spray RR = 1.9 95 CI 1.1-3.1 These results offer support for the hypothesis raised by prior epidemiologic studies that powder exposure from perineal dusting contributes to the development of ovarian cancer and they suggest that use of genital deodorant sprays may do so as well Limitations of the present study include the fairly low proportion of eligible women who participated and the potential differential recall of powder usage Am J Epidemiol 459 65 ovarian neoplasms powders talc asoline a 111-14 ernational 1995 . InternaJ Cancer e Copen- ncer role er 1988 rol study s Am J er of the idy Br on State | Human pational plement lajesty's pational lon Her tigation ons and 971 14 onserva- gasoline 4/87 ige mens from 94 Studies documenting the migration of carbon parti- cles and radioactive particulate agents from the vagina to the ovaries 1 2 as well as those that have iden- tified like particles more frequently in ovarian tumors than in normal human ovarian tissue 3 have raised concern that genital powder exposure may increase a woman's risk of developing ovarian cancer While the results of several epidemiologic studies have suggested elevated risks for ovarian cancer among women with genital powder exposures 4-11 results have been inconsistent for particular methods of powder application 12 In this population control study information on the method dura- tion and frequency of powder application was collected to evaluate the impact of genital powder exposures on the risk of epithelial ovarian cancer MATERIALS AND METHODS Women with invasive or borderline epithelial ovar- ian cancer were identified from records of the popu- Received for publication May 20 1996 and accepted for publication October 22 1996 Abbreviations Cl confidence interval RR relative risk 1 Fred Hutchinson Cancer Research Center Seattle WA 2 Department of Epidemiology University of Washington tle WA Seat- Reprint requests to Dr. Linda S. Cook 381 Fred Hutchinson Cancer Research Center 1124 Columbia Street Seattle WA 98104 based Cancer Surveillance System of western Washington Eligible case subjects included white women diagnosed between January 1 1986 and December 31 1988 who resided in three counties of western Washington King Pierce and Snohomish counties and were 20-79 years of age at diagnosis After obtaining permission from their personal physi- cians to contact the women and obtaining written informed consent we successfully interviewed 329 64.3 percent of the 512 eligible case subjects The remaining 183 women were not interviewed because of death prior to study contact n = 104 20.3 percent physician or subject refusal n = 73 14.3 percent and lack of success in locating the women n = 6 1.2 percent Seven women whose reported race ethnicity was other than white and nine women with unknown genital powder use were also excluded Thus a total of 313 white women diagnosed with borderline n = 79 or invasive n = 234 epithelial ovarian tumors were available for analysis Women identified as control subjects for this study were part of a larger control pool selected by random digit dialing 13 for several studies of cancer in women Of the total 10,109 calls made by random digit dialing 5,853 57.9 percent were to nonresidential phone numbers 3,830 37.9 percent were to residential phone numbers and 426 4.2 percent were to , 1997 ] 459 The material on this cag be page FOES was copied from t the re #F colection of TE the National Library te of eee Medicne by a third 4 party and eae may be er protected by U.S. Copyright law 460 Cook et al ee law AGAR Copyright U.S. by protecd be may BL and party BAM i third WME aaed by Ra Medicne ARE et Laie of Library Library National aaeT the ne of MT Ce s Pecolection the from B^ S copied B^S ^ R^ S was ^ R^ S STAM page MATORKE this MATORKE on material The numbers of unknown residential status 3,604 94.1 percent of the 3,830 calls to residential households were screened for eligible women who were age matched in year age groups to the combined female cancer case group Of the 721 women identified who were eligible 521 72.3 percent were successfully interviewed after written informed consent was ob- tained The overall response random digit dialing screening response multiplied by the interview response was 68.0 percent Women who reported race ethnicity other than white n = 28 age greater than 79 n = 5 a history of bilateral oophorectomy n = 58 uncertainty concerning a history of bilateral oophorectomy n = 4 and unknown genital powder use n = 4 were excluded resulting in a total of 422 white control women for analysis Information regarding genital powder exposures was collected by structured person interviews Women were queried about storing diaphragms in powder dusting perineal areas with powder after bathing powdering sanitary napkins and using genital deodorant sprays which may contain aerosolized powder Those who answered affirmatively were questioned further about the duration and frequency of powder application and about the types of powder applied Powders were grouped into five categories cornstarch talcum powder baby powder deodorant powder and scented body powder Information on demographic characteristics reproductive history medical and screening histories smoking history anthropometry and birth control methods was also provided by the women A calendar was used to record major life events and enhance recall of past exposures Relevant study information was recorded only for exposures that occurred prior to the diagnosis date of cancer among the cases or the analogous reference date among controls Logistic regression EGRET version 26.6 Statistics and Epidemiology Research Corporation Seattle Washington was used to determine odds ratios as estimates of the relative risk for ovarian cancer asso- ciated with genital powder application and 95 percent confidence intervals 14 For all the relative risk estimates reported in the present analysis women who reported any method type or frequency of genital powder application were compared with women who stated that they had never applied genital powder in any manner 154 ovarian cancer cases and 256 con- trols Trends were evaluated using the likelihood ratio statistic 14 First the relative risk for ovarian cancer among women who reported exclusive use of one of the four methods of powder application was assessed table 2 Then because many women used more than one method of powder application the risk for ovarian cancer among women who reported any use of the four methods of powder application was assessed while adjusting for the other methods of powder application table 3 Similarly ovarian cancer risk by exclusive and nonexclusive use of the type of powder used for perineal dusting diaphragm storage or on sanitary napkins was assessed table 4 To assess the impact of genital powder exposure on the risk of specific histologic categories of ovarian tumors table 5 we grouped borderline and invasive ovarian tumors according to the following International Classification of Diseasefosr Oncology histologic codes 15 serous tumors codes 8441 8442 8460 8461 and 8462 mucinous tumors codes 8470 8472 8473 8480 and 8481 endometrioid tumors codes 8380 8381 and 8560 and other tumors that included clear cell code 8310 undifferentiated code 8020 and unclassified other codes 8010 8050 8140 8240 8260 8440 8450 and 9000 All relative risk estimates were adjusted for age Further adjustment for education income marital status body mass index weight kg height m oral contraceptive use or parity did not alter the estimated relative risks Information on lac- tation was not available Separate analyses for women diagnosed with invasive ovarian cancer and for those diagnosed with borderline ovarian cancer produced results very similar to those presented in tables 2-5 RESULTS Selected characteristics of ovarian cancer cases and controls are presented in table 1. Less education a lower household income and a higher body mass index were more common among women with ovarian cancer than among control women but oral contracep- tive use and having had a term birth were less common Genital powder application was more common among cases 50.8 percent than controls 39.3 percent table 2 There was an overall 50 percent ele- vation in the risk for ovarian cancer associated with the use of one or more of the four possible methods of genital powder application 95 percent CI 1.1-2.0 Among women who exclusively used a single method of powder application ovarian cancer risk was most strongly elevated among those who dusted perineal areas with powder after bathing RR = 1.8 95 percent CI 1.2-2.9 We further examined ovarian cancer risk among women who reported application of genital powders using each of the four methods although not necessarily exclusive use of any method table 3 Perineal dusting was associated with an increased risk of ovar- Am J Epidemiol Vol 145 No. 5 1997 ian can though with inc tribution tubal li relative shown untary powder cancer : 1976 or 1977 or in 1976 Am J Ep Powder and Ovarian Cancer 461 varian e four while ication lusive sed for initary pact of histo- ) we ors ac- cation serous 8462 0 and 1 and : code ssified 8440 adon in- t kg lid not on lac- vomen : those duced . 2-5 es and tion a " mass varian tracepre less ommon .3 pernt eled with ods of 2.0 method s most erineal percent among owders neces- erineal of ovar- 5. 1997 TABLE 1. Characteristics of epithelial ovarian cancer cases and controls King Pierce and Snohomish counties Washington State 1986-1988 Characteristic Age years 20-34 35-44 45-54 55-64 65-79 Education years /8 9-12 13-16 16 Unknown Annual household income $ 15,000 15,000-30,000 30,000-45,000 ; 45,000 Unknown Marital status Single Married Separated Body mass index m 21 21-22 23-24 25 Oral contraceptive use Never or /1m2onths 12 months but 5 years 25 years Total pregnancies 0 1 > Unknown Total term births 0 1 2 Unknown Cases n 313 No. % JO JO 60 88 81 DIN124 146 DINDIN- 85689 85689 85689 85689 85689 32 186 95 6225 6225 6225 6225 224 23 23 57 27 214 0 79 46 188 0 10.9 16.0 19.2 28.1 25.9 4.8 39.6 46.6 8.6 0.3 28.8 29.1 19.2 20.1 2.9 10.2 59.4 30.4 17.9 28.4 23.3 30.4 71.6 16.0 12.5 18.2 13.4 68.4 25.2 14.7 60.1 Controls n 422 No. % 84 136 NOR NOR NOR 14 144 ONE ONE 0 83 153 81 96 9 33 292 97 97 145 75 105 221 93 108 56 56 309 1 83 69 269 1 19.9 32.2 15.4 14.9 17.5 3.3 34.1 51.9 10.7 19.7 36.3 19.2 22.7 2.1 7.8 69.2 23.0 23.0 34.4 17.8 24.9 52.4 22.0 25.6 13.3 13.3 73.2 0.2 19.7 16.4 63.7 0.2 ian cancer RR = 1.6 95 percent CI 1.1-2.3 although there was no clear pattern of increasing risk with increasing duration of use When the small contribution of perineal dusting after a hysterectomy or tubal ligation was excluded from the analysis our relative risk estimates were nearly unchanged data not shown In 1976 the cosmetic industry proposed voluntary guidelines to limit contamination of consumer powders 16 and we attempted to evaluate ovarian cancer risk associated with any perineal dusting in 1976 or before and with exclusive perineal dusting in 1977 or thereafter Women with any perineal dusting in 1976 or before had an elevated risk RR = 1.8 95 Am J Epidemiol Vol 145 No. 5 1997 percent CI 1.1-2.9 but we were unable to evaluate exclusive perineal dusting in 1977 and thereafter since only four cases and 10 controls had this exposure The use of genital deodorant sprays was also associated with an elevated ovarian cancer risk RR = 1.9 95 percent CI 1.1-3.1 with the strongest elevation in risk among the small number of women n = 15 who used these sprays for more than 1 year RR = 2.7 95 percent CI 1.1-6.6 Storing a diaphragm in powder or powdering sanitary napkins was not related to the risk of developing an ovarian tumor RR = 1.0 95 percent CI 0.6-1.6 and RR = 0.9 95 percent CI 0.5-1.5 respectively The material on this 3 page was copied from the colectiona: collection WY of ** the National $ National Library of Medicine by a third party and may be % protec d by US Copyright law 462 Cook et al law TABLE 2 Relative risk of epithelial ovarian cancer associated with exclusive use of various methods of any genital powder use and by Washington State 1986-1988 powder applicationapplication King Pierce and Snohomish counties Copyright Ovarian cancer casescases application cancer 313 = Controls n = 422 RR 95 CI U.S. No. % No. % by Lifetime genital powder application None Any 154 49.2 256 60.7 1.0 159 50.8 166 39.3 1.5 Referent 1.1-2.0 protec d Exclusive use of be Perineal dusting only 55 17.6 00100000 11.4 1.8 1.2-2.9 may Diaphragm storage in powder only 22 7.0 00100000 8.3 0.8 and Powder on sanitary napkins only 12 3.8 00100000 2.4 1.5 0.4-1.4 0.6-3.6 Genital deodorant spray only 18 5.8 00100000 6.6 1.5 0.8-3.0 party * RR relative risk adjusted for age CI confidence interval third a by No specific type of powder used for perineal dust- tent of talc asbestiform minerals or ing diaphragm storage or on sanitary napkins was ilar structurally sim- compounds Powder content has also varied over strongly related to ovarian cancer risk although there time presumably with fewer asbestiform minerals Medicne was a suggestion of an elevated risk associated with present in more recently manufactured products 17- of any use of talcum powder and body powders 19 RR = 1.6 95 percent CI 0.9-2.8 and RR = 1.5 95 CI 0.9 2.r4espectively table 4 When Our results suggest that a history of perineal dusting percent Library cific histologic categories of ovarian tumors spe- or use of genital deodorant sprays has a modest influ- amined any genital powder application were ex- associated ence on the development of epithelial ovarian tumors with an elevated risk for was whereas storing a diaphragm in powder or powdering National CI serous tumors RR = 1.7 95 sanitary napkins does not Direct comparisons of our the percent 1.1-2.5 and the nonspecific category of results with those of the other nine of other tumors RR = 1.8 95 percent CI 1.1 2.8 published studies and among these studies are somewhat limited be- whereas no elevation in risk was noted for the small number of with cause of differences in the definitions groupings and women mucinous tumors RR = 0.7 colection 95 percent CI 0.4-1.4 or endometrioid tumors RR = analysis of genital powder use Nonetheless there is the 1.2 95 percent CI 0.6-2.3 table 5 some consistency in results among studies Seven studies including the present one 4 6 8-11 ) reported from DISCUSSION elevated relative risks for ovarian cancer ranging from 1.3 to 3.9 among women with powder exposure by copied There are several issues that should be considered in dusting of the perineum Of the three remaining the interpretation of our results A sizable number of studies that evaluated the more general exposure of was women eligible for our study did not participate par- talc use in perineal area which may or may ticularly among those with ovarian cancer Many not include perineal sanitary napkin diaphragm or page women with cancer died before they could be ap- undergarment applications two observed a modest this proached about participation in this study and others elevation in ovarian cancer risk 5 7 whereas one did on were too ill to participate If substantial differences in not 20 powder use existed between participating and nonparticipating women our study results may over- or un- material derestimate the true risks for ovarian cancer It is also The possible that the completeness of the reporting of powder use differed between cases and controls bias- ing our relative risk estimates to some degree Additionally it is not clear how well ascertainment of perineal powder application correctly estimates actual exposure to particles in powder that may influence ovarian cancer risk Different consumer brands of powder that women used or even different lots of the Most studies including the present one have found little if any excess risk for ovarian cancer among women who stored their diaphragms in powder 4-8 10 only one study has reported a suggestion of an elevation in risk 11 In the present study control women more frequently reported washing their diaphragms prior to use than did ovarian cancer cases but ovarian cancer risk was not substantially elevated for the small number of women who did not wash their diaphragms prior to use The relation between powdering sanitary napkins and ovarian cancer risk is less same brand may have varied substantially in the con- clear three studies including the present study found Am J Epidemiol Vol 145 No. 5. 1997 Powder and Ovarian Cancer 463 TABLE 3 Relative risk of epithelial ovarian cancer associated with genital powder use by methods of powder application King Pierce and Snohomish counties Washington State 1986 1988 Lifetime genital powder application Ovarian cancer cases n 313 No. % Controls n 422 No. % RR 95 Cit None 154 49.2 256 60.7 1.0 Referent Any perineal dusting 95 30.4 87 20.6 1.6 1.1-2.3 The Cumulative lifetime days The /2,000 2228 6.4 22 5.2 1.8 0.9-3.5 2,001-5,000 5,001-10,000 2228 7.7 26 2228 6.7 22 6.2 1.6 5.2 1.2 0.9-2.9 0.6-2.4 material 10,000 2228 8.9 17 4.0 1.8 0.9-3.4 on Unknown 2 0.6 0 this Diaphragm storage in powder Cumulative lifetime months 46 14.7 115656 12.1 1.0 0.6-1.6 page was /60 60 27 7.7 225 6.2 1.1 27 4.8 225 4.7 0.6-1.9 0.4-1.7 copied ver Unknown Usually washed before use No 27 2.2 225 19 6.1 +36 1.2 3.3 1.4 0.7-3.0 als Yes 20 6.4 +36 7.3 0.7 0.4-1.4 from the Unknown 7 2.2 +36 1.4 Any powder on sanitary napkins 801- 12.1 40 9.5 0.9 0.5-1.5 colection ing Cumulative lifetime months 120 801- 8.0 21 5.0 1.3 0.7-2.4 ors 120 801- 3.8 19 4.5 0.5 0.2-1.1 of the ing Unknown Lifetime applications 801- 0.3 0 Our /1,000 37- 7.3 19 2009 1.3 0.7-2.5 ies be- 1,000 Unknown 37- 4.5 21 2009 0.6 37- 0.3 0 0.3-1.2 National ind Any genital deodorant spray Cumulative lifetime months 40 12.8 40 9.5 1.9 1.1-3.1 Library en 12 24 7.7 31 7.4 1.5 0.9-2.8 of ted 12 15 4.8 9 2.1 2.7+ 1.1-6.6 Medicne om Unknown 1 0.3 0 Lifetime applications by /500 20 9.3 34 8.1 1.7 1.0-2.9 by .ng 500 20 3.2 ... 1.4 2.6+ 0.9-7.6 a of Unknown 1 0.3 0 third Tay * Numbers do not add up to total cases and controls because women may have used a variety of methods for or party est and lid powder application RR relative risk adjusted for age and for the other methods of genital powder application none any CI confidence interval + p value for trend < 0.05 may and be no association 6 10 whereas three other studies powder and body powders among women using protec d reported moderate elevations in risk 4 8 11 these powders for perineal dusting diaphragm storage an Only two other studies have evaluated particular or on sanitary napkins rol types of powder one reported an excess risk of bor- The present study is the first to evaluate the associ- by US derline ovarian tumors among women who used de- ation between genital deodorant spray use and ovarian out odorant powders 8 and another study reported an cancer risk these preliminary results require confir- Copyright for excess risk of ovarian cancer among women who used mation in other studies It is difficult to postulate that eir baby powders 10 A strong relation between the an increased risk for ovarian cancer may specifically W- types of powder used and ovarian cancer risk was not be due to powder and associated constituents when ess found in the present study although there was a sug- some of the deodorant sprays do not contain aerosol- law ind gestion of an elevated risk with any use of talcum ized powder It is possible that it is not powder per se 997 Am J Epidemiol Vol 145 No. 5 1997 hat may er is un- n fibrous hydrous all body cifically fibrous e across the skin is parti- " can be is rela- include in open moconi- 5 1997 Powder and Ovarian Cancer 465 osis talcosis in individuals with term exposure to talc dust 19 Occupational exposure to talc does not appear to increase the risk for pulmonary malig- nancies 19 Most animal studies confirm this with lung tumors developing only in rats exposed to doses of talc dust high enough to cause chronic obstructive and restrictive lung toxicity 19 Excess ovarian tu- mors have not been reported in rats and mice with term exposure to aerosol talc 23 In contrast occupational exposure to asbestos fibers has been shown to cause lung tumors 24 and has been asso- ciated with the development of ovarian tumors 25 Thus while there is little biologic or experimental evidence to support a role for talc per se in the devel- opment of ovarian malignancies the potential biologic effects of consumer powders with their variable con- stituents on the human ovary have not been well studied The prevalence of genital powder exposure reported among control women in this and other studies conducted in the United States ranges from 28 percent to 51 percent 4-6 8 10 Given such a common practice even the modest elevation in ovarian cancer risk associated with genital powder application suggested by most of the epidemiologic studies could have a notable impact on the incidence of ovarian cancer in the United States We recommend that cohort studies address this question these studies could eliminate concerns regarding the potential differences in the reporting of genital powder exposures between cases and con- trols We also believe that further characterization of the constituents of powder products that may influence ovarian cancer risk and the investigation of their possible biologic mechanisms of carcinogenesis are warranted 2. Ventor PF Iturralde M. Migration of a particulate radioactive tracer from the vagina to the peritoneal cavities and ovaries S Afr Med J 917 19 3. Henderson WJ Joslin CA Turnbull AC et al Talc and carcinoma of the ovary and cervix J Obstet Gynaecol Br Commonw 266 72 4. Cramer DW Welch WR Scully RE et al Ovarian cancer and talc a control study Cancer 372 6 5. Hartge P Hoover R Lesher LP et al Talc and ovarian cancer Letter JAMA 1844 6. Whittemore AS Wu ML Paffenbarger RS Jr et al Personal and environmental characteristics related to epithelial ovarian cancer II Exposures to talcum powder tobacco alcohol and coffee Am J Epidemiol 1228-40 7. Booth M Beral V Smith P. Risk factors for ovarian cancer a J control study Br Cancer 592 8 8. Harlow BL Weiss NS A control study of borderline ovarian tumors the influence of perineal exposure to talc Am J Epidemiol 390-4 9. Chen Y Wu PC Lang JH et al Risk factors for epithelial ovarian cancer in Beijing China Int J Epidemiol 1992 23-9 The The wos material on this page was 10. Harlow BL Cramer DW Bell DA et al Perineal exposure to talc and ovarian cancer risk Obstet Gynecol 19-26 11. 11. Rosenblatt KA Szklo M Rosenshein NB Mineral fiber ex- posure and the development of ovarian cancer Gynecol Oncol 20-5 12. Harlow BL Hartge PA A review of perineal talc exposure and risk of ovarian cancer Regul Toxicol Pharmacol 1995 254-60 13. Waksberg J. Sampling methods for random digit dialing J Am Stat Soc 40-6 Lyon 14. Breslow NE Day NE eds Statistical methods in cancer research Vol 1. The analysis of control studies International Agency for Research on Cancer 1980. IARC scientific publication no 32 15. World Health Organization International classification of diseases for oncology 2nd ed Geneva World Health Organization 1990 16. Cosmetic Toiletry and Fragrance Association CTFA Talc specification and methods In CTFA compendium of cosmetic ingredient composition Washington DC CTFA 1976 10-17 copied from ag the get: colection eo of cst the ora 2B National Library of 17. Cralley LJ Key MM Groth DH et al Fibrous and mineral content of cosmetic talcum products Am Ind Hyg Assoc J 350-4 Medicine ACKNOWLEDGMENTS This research was supported by grant R35 CA39779 from the National Cancer Institute and by the Cancer Surveil- lance System of the Fred Hutchinson Cancer Research Center which is funded by contract no 05230 from the Surveillance Epidemiology and End Results SEER Program of the National Cancer Institute with ad- 18. Rohl AN Langer AM Selikoff IJ et al Consumer talcums and powders mineral and chemical characterization J Toxicol Environ Health 255-84 19. Zazenski R Ashton WH Briggs D et al Tale occurrence characterization and consumer applications Regul Toxicol Pharmacol 218-29 20. Tzonou A Polychronopoulou A Hsieh C et al Hair dyes 408-10 analgesics tranquilizers and perineal tale application as risk factors for ovarian cancer Int J Cancer 408-10 21. Kasper CS Chandler PJ Possible morbidity in women from talc on condoms JAMA 846-7 by a third p$arty and may be ditional support from the Fred Hutchinson Cancer Research Center The authors thank Kay Byron and Judy Kuskin for their 22. Paoletti L Caiazza S Donelli G et al Evaluation by electron protec d microscopy techniques of asbestos contamination in indus- 3 trial cosmetic and pharmaceutical tales Regul Toxicol Phar- macol 222 35 programming assistance Diana Farrow for assistance with data collection and Robert C. Lee for his review of the manuscript and insightful comments REFERENCES 151 1. Egli GE Newton M. The transport of carbon particles in the human female reproductive tract Fertil Steril 23. 24. 25. 5 National Toxicology Program NTP Toxicology and carcinogenesis studies of talc in F344 rats and B6C3F mice inhalation studies Research Triangle Park NC US Depart- ment of Health and Human Services 1993. NIH publication no 93-3152 Roggli VL Human disease consequences of fiber exposures a review of human lung pathology and fiber burden data Environ Health Perspect 295 303 Weiss NS Cook LS Farrow DC et al Ovary In Schottenfeld D Fraumeni JF eds Cancer epidemiology and prevention 2nd ed New York Oxford University Press 1996 by U.S. U.S. Copyright law Am J Epidemiol Vol 145 No. 5 1997